DESCRIPTION: Ischemic heart disease (IHD) is the number one cause of death in western societies. A rapid and noninvasive method of early detection of myocardial underperfusion would be important for the timely institution of therapy, but no method to date has provided reliable, high-resolution detection MRI is a noninvasive technique with excellent soft tissue resolution. For IHD, however, it is hampered by the lack of sufficient intrinsic contrast. With specific contrast agents MRI would enable the early detection of perfusion abnormalities. Existing agents, however, are not specific enough nor are retained long enough to allow stress-coupled MRI of perfusion. We have designed and synthesized effective new agents. Three have passed the in vitro tests Gd(BME-DTTA), Gd(MHE-DTTA), and "ELGAVIST." We have shown that Gd(BME- DTTA) creates detectable MRI contrast of underperfused myocardium in images of LAD- occluded ferrets and dogs, in vivo, but it requires liposomic dispersion. Its best water-soluble analog, "ELGAVIST," is the most likely to gain commercial success. Thus the goal of the present proposal is the small- scale study (Phase I) of "ELGAVIST" efficacy in the in vivo experimental dog model of acute myocardial ischemia followed by reperfusion, with and without dobutamine-induced pharmacologic stress. The results would likely lead to a more detailed Phase II which should establish the clinical potential of "ELGAVIST" for early diagnosis of IHD with a market potential larger than that of Thallium or Cardiolite.